Cytokine Treatment of Radiation-Induced Hemopoietic Suppression: Results of Interleukin-6 and Granulocyte Colony-Stimulating Factor in a Murine Radiation Model

Abstract

Following accidental radiation exposure or intensive radiotherapy severe hemopoietic depression often results from damage to hemopoietic stem and progenitor cell populations. The major risks of mortality following radiation exposure are sepsis (resulting from a lack of granulocytes) and hemorrhage (resulting from a lack of platelets). In recent years a variety of recombinant cytokines have been shown to possess hemopoietic activity [1, 2]. In particular, the ability of interleukin-6 (IL-6) to stimulate multilineage stem cell production [3–5] and the ability of granulocyte colony-stimulating factor (G-CSF) to enhance granulocyte production and function [6–8] have been demonstrated in vitro. Based on these effects, we hypothesized that in vivo IL-6 administration may amplify multilineage stem cell production, which if followed by G-CSF administration to induce multilineage cells towards granulocyte production, could provide an effective treatment for radiation- or drug-induced hemopoietic suppression. Before beginning such studies, however, it was necessary to evaluate the in vivo effects of each cytokine. The studies presented in this paper describe the ability of IL-6 and G-CSF to individually stimulate hemopoietic regeneration in vivo following radiation- induced hemopoietic injury in mice.